Akeso's Cadonilimab Enters Pivotal Perioperative Gastric Cancer Trial: A Strategic Step Toward Expanding Market Reach and Investment Value

In the evolving landscape of oncology, few innovations have captured the attention of investors and clinicians alike as effectively as Akeso Inc.'s (9926.HK) cadonilimab, a first-in-class PD-1/CTLA-4 bispecific antibody. With gastric cancer remaining a global health burden—accounting for over 1 million new cases annually—the unmet need for therapies that transcend PD-L1 expression limitations has never been more urgent. Cadonilimab's recent foray into the COMPASSION-33 trial for perioperative gastric cancer marks a pivotal moment, not just for Akeso, but for the broader immunotherapy market.

Clinical Breakthroughs: Redefining Gastric Cancer Treatment

Cadonilimab's clinical differentiation lies in its ability to deliver consistent survival benefits across all PD-L1 expression levels. The landmark COMPASSION-15 trial demonstrated a 38% reduction in mortality risk (HR 0.62) for advanced gastric cancer patients, even in PD-L1 low/negative subgroups where traditional PD-1 inhibitors falter. This is a critical advantage, as approximately 60% of gastric cancer patients fall into PD-L1 low/negative categories.

The neoadjuvant trial further solidified its potential: a 100% R0 resection rate and 44.7% major pathological response (MPR) in locally advanced cases, regardless of PD-L1 status. These results suggest cadonilimab could revolutionize pre-surgical protocols, addressing a therapeutic gap where no approved immunotherapy currently exists.

Strategic Expansion: From Advanced to Perioperative Settings

The launch of COMPASSION-33—a Phase III trial evaluating cadonilimab in combination with chemotherapy for perioperative gastric cancer—represents a masterstroke in Akeso's market strategy. By targeting earlier-stage disease, the company is not only expanding its therapeutic footprint but also positioning cadonilimab as a first-line perioperative standard. This trial could unlock a new revenue stream, as perioperative regimens are typically administered to healthier, more numerous patient populations compared to advanced-stage therapies.

Moreover, Akeso is exploring cadonilimab in second-line settings for PD-1-resistant patients, combining it with a VEGFR-2 inhibitor. This dual-combination approach addresses treatment resistance, a persistent challenge in gastric cancer, and further cements cadonilimab's role as a cornerstone therapy.

Commercial Positioning: First-in-Class Leadership and Market Access

Akeso's commercial acumen is equally impressive. The inclusion of cadonilimab in China's National Reimbursement Drug List (NRDL) has accelerated adoption, reducing patient out-of-pocket costs and boosting hospital access. The company's aggressive infrastructure investments—such as expanding its sales force and engaging key opinion leaders—have amplified market penetration.

Competitively, cadonilimab's first-in-class status and broad PD-L1 efficacy give it a clear edge over PD-1 monotherapies like Merck's Keytruda or Bristol-Myers Squibb's Opdivo, which show limited efficacy in PD-L1-negative patients. With over 30 ongoing trials across 16 indications, Akeso is leveraging cadonilimab's versatility to dominate the bispecific antibody space.

Investment Implications: A High-Conviction Play

For investors, Akeso's cadonilimab represents a high-conviction opportunity. The drug's clinical success in gastric cancer, combined with its expansion into cervical, lung, and liver cancers, creates a multi-billion-dollar revenue potential. The recent NRDL inclusion and favorable safety profile further reduce commercial risks.

However, risks remain. Regulatory hurdles in global markets and competition from emerging bispecific antibodies (e.g., Merck's bintrafusp alfa) could temper growth. Yet, Akeso's first-mover advantage in gastric cancer and its robust clinical data provide a strong moat.

Conclusion: A Catalyst for Long-Term Growth

Akeso's cadonilimab is more than a drug—it's a paradigm shift in gastric cancer treatment. By addressing PD-L1-negative patients and expanding into perioperative settings, the company is redefining the boundaries of immunotherapy. For investors seeking exposure to a first-in-class innovation with clear commercial pathways, Akeso's stock offers compelling upside. As COMPASSION-33 progresses and global approvals materialize, the investment thesis strengthens.

Final Verdict: Akeso's strategic execution and cadonilimab's clinical differentiation make it a must-watch stock in 2025. Investors with a 3–5 year horizon should consider a long position, particularly as the company navigates key regulatory and trial milestones.